title: Advances in myelofibrosis: a clinical case approach.
abstract: Primary myelofibrosis is a member of the myeloproliferative neoplasms, a diverse group of bone marrow malignancies. Symptoms of myelofibrosis, particularly those associated with splenomegaly (abdominal distention and pain, early satiety, dyspnea, and diarrhea) and constitutional symptoms, represent a substantial burden to patients. Most patients eventually die from the disease, with a median survival ranging from approximately 5-7 years. Mutations in Janus kinase 2 (JAK2), a kinase that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 50% of patients with myelofibrosis. The approval of a JAK2 inhibitor in 2011 has improved the outlook of many patients with myelofibrosis and has changed the treatment landscape. This article focuses on some of the important issues in current myelofibrosis treatment management, including differentiation of myelofibrosis from essential thrombocythemia and polycythemia vera, up-dated data on the results of JAK2 inhibitor therapy, the role of epigenetic mechanisms in myelofibrosis pathogenesis, investigational therapies for myelofibrosis, and advances in hematopoietic stem cell transplant. Three myelofibrosis cases are included to underscore the issues in diagnosing and treating this complex disease.
authors.affiliation: john.mascarenhas@mssm.edu.
authors.forename: John O
authors.initials: JO
authors.lastname: Mascarenhas
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Kapil N
authors.initials: KN
authors.lastname: Bhalla
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
authors.forename: Ronald
authors.initials: R
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage; D011743:Pyrimidines
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2